“Soluble Tissue Factor” in the 21st Century: Definitions, Biochemistry, and Pathophysiological Role in Thrombus Formation

Abstract

Tissue factor (TF), the main trigger of blood coagulation, is essential for normal hemostasis. Over the past 20 years, heightened intravascular levels and activity of TF have been increasingly perceived as an entity that significantly contributes to venous as well as arterial thrombosis. Various forms of the TF protein in the circulation have been described and proposed to be thrombogenic. Aside from cell and vessel wall-associated TF, several forms of non–cell-associated TF circulate in plasma and may serve as a causative factor in thrombosis. At the present time, no firm consensus exists regarding the extent, the vascular setting(s), and/or the mechanisms by which such TF forms contribute to thrombus initiation and propagation. Here, we summarize the existing paradigms and recent, sometimes paradigm-shifting findings elucidating the structural, mechanistic, and pathophysiological characteristics of plasma-borne TF.

Beyond thrombosis: the impact of tissue factor signaling in cancer

“…TF localizes to lamellipodia, which are created by cytoskeletal protein actin projections on the invasive edges of cells [ 61 – 63 ]. TF binding of ABP-280 may also positively regulate its release via flTF-MVs [ 64 ], resulting in paracrine signaling [ 65 ]. The flTF cytoplasmic domain is phosphorylated at Ser253 by protein kinase C (PKC) and at Ser258 by p38 MAPK [ 28 , 31 , 36 , 66 ].…”

Molecularly engineered truncated tissue factor with therapeutic aptamers for tumor-targeted delivery and vascular infarction

“…It has been shown that the ability of tTF to activate FX is greatly reduced, compared to full-length tissue factor. Therefore, placing tTF in proximity to a phospholipid membrane is essential to recover its potent coagulation activity 15 , 16 , 17 , 18 , 19 , 20 . In consideration of this property, peptide ligands or antibodies that recognize different tumor endothelial markers have been fused to tTF to specifically deliver this protein to tumor vessels for tumor infarction 6 , 7 , 8 , 9 , 10 , 11 .…”

Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes

“…Subsequent TF-triggered coagulation contributes to arterial thrombosis and acute coronary syndrome 7,8 . Blood-borne TF may also contribute to intravascular coagulation and thrombosis 9,10 . Monocytes are a central source of blood-borne TF following inflammatory or infectious stimuli 4,11,12 .…”